Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


Modulation of Monocyte Response by Microrna-15b/106a/374a During Antibody-mediated Rejection in Kidney Transplantation.


BACKGROUND: Increasing evidence suggest that microRNAs are involved in the physiopathology of acute or chronic renal disease. In kidney transplantation, as key regulators of cellular homeostasis, microRNAs may be involved in the regulation of immune cell function and the allograft response. Here, we investigated the change in circulating microRNA expression profile and their involvement in the profound transcriptional changes associated with antibody-mediated rejection (ABMR). METHODS: Blood samples were collected at the time of the 710 kidney allograft biopsies at 4 European transplant centers. Messenger RNA and microRNA profiling analyses were performed in a discovery-to-validation study within 3 independent cohorts encompassing N = 126, N = 135, and N = 416 patients, respectively. RESULTS: Compared with samples with no ABMR, 14 microRNAs were significantly decreased in ABMR samples. Among them, expression levels of microRNA-15b, microRNA-106a, and microRNA-374a gradually decreased with the severity of ABMR lesions. From their in silico-predicted target genes, a high proportion proved to be significantly upregulated in the paired transcriptomic analysis. Gene ontology analyses of microRNA-15b/-106a/-374a suggested enrichment in myeloid-related pathways, which was further refined by in silico and ex vivo transcriptomic analyses, showing a specific origin from classical CD14+ monocytes. Finally, human CD14+ monocytes were subjected to transduction by antago-microRNAs to mimic ABMR pathology. MicroRNA-15b/-106a/-374a impairment resulted in cellular activation with an increased expression of CD69, CRIM1, IPO7, and CAAP1, direct and common targets of the 3 microRNAs. CONCLUSIONS: Together, our data provide new insights into circulating microRNAs as markers and key players in ABMR, and they suggest monocyte involvement in this process.

Authors: Tinel C, Lamarthée B, Gazut S, Van Loon E, Von Tokarski F, Benon A, Sauvaget V, Garcia-Paredes V, Ménager M, Morin L, Aouni L, Cagnard N, Rabant M, Legendre C, Terzi F, Essig M, Gwinner W, Naesens M, Marquet P, Anglicheau D,
Journal: Transplantation;2022Nov04. doi:10.1097/TP.0000000000004393
Year: 2022
PubMed: PMID: 36398319 (Go to PubMed)